Cited by 474CRISPR and Genetic EngineeringRNA regulation and diseasePluripotent Stem Cells Research

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Low Incidence of Off-Target Mutations in Individual CRISPR-Cas9 and TALEN Targeted Human Stem Cell Clones Detected by Whole-Genome Sequencing

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Veres, Adrian, Gosis, Bridget S., Ding, Qiurong, Collins, Ryan, Ragavendran, Ashok, Brand, Harrison, Erdin, Serkan, Cowan, Chad A., Talkowski, Michael E., Musunuru, Kiran·2014·Cell Stem Cell

DOI 10.1016/j.stem.2014.04.020PMC PMC4082799

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Abstract

Genome editing has attracted wide interest for the generation of cellular models of disease using human pluripotent stem cells and other cell types. CRISPR-Cas systems and TALENs can target desired genomic sites with high efficiency in human cells, but recent publications have led to concern about the extent to which these tools may cause off-target mutagenic effects that could potentially confound disease-modeling studies. Using CRISPR-Cas9 and TALEN targeted human pluripotent stem cell clones, we performed whole-genome sequencing at high coverage in order to assess the degree of mutagenesis across the entire genome. In both types of clones, we found that off-target mutations attributable to the nucleases were very rare. From this analysis, we suggest that, although some cell types may be at risk for off-target mutations, the incidence of such effects in human pluripotent stem cells may be sufficiently low and thus not a significant concern for disease modeling and other applications.

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Self-citation

Authors: Veres, A., Gosis, B. S., Ding, Q., Collins, R., Ragavendran, A., Brand, H., Erdin, S., Cowan, C. A., Talkowski, M. E., & Musunuru, K.
Affiliations: Harvard University (US)
Massachusetts General Hospital (US)
Broad Institute (US)
Corresponding author: Musunuru, Kiran
ORCID: Veres, Adrian
Gosis, Bridget S.
Ding, Qiurong
Collins, Ryan
Ragavendran, Ashok
Brand, Harrison
Erdin, Serkan
Talkowski, Michael E.
Musunuru, Kiran
Venue: Cell Stem Cell
Publisher: Elsevier BV
Published: 2014-07
Volume: 15
Issue: 1
Pages: 27-30
ISSN: 1875-9777 (ISSN-L)
1934-5909
DOI: 10.1016/j.stem.2014.04.020
PMC: PMC4082799
OpenAlex: W1974343902
Cited by: 474
References: 32
Citations by year: 2026: 6 · 2025: 8 · 2024: 10 · 2023: 24 · 2022: 24 · 2021: 32 · 2020: 33 · 2019: 43 · 2018: 46 · 2017: 61 · 2016: 72 · 2015: 86 · 2014: 29
FWCI: 33.92
Type: journal article
Language: en
Update notices: erratum (2014-08-07)
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 367 d)
Locations: Cell stem cell (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
Funders: National Heart, Lung, and Blood Institute (U01HL100408, R00HL098364, R01HL118744)
National Institute of Mental Health (R00MH095867)
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK097768)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
Keywords: off-target mutations, CRISPR/Cas9, TALEN, genome editing, human pluripotent stem cells, mutagenesis, disease modeling, whole genome sequencing
MeSH terms: Sortilin, Base Sequence, Clone Cells, Endonucleases, Genetic Engineering, Humans, Molecular Sequence Data, Mutation, Organ Specificity, Incidence, Genome, Sequence Analysis, DNA, Adaptor Proteins, Vesicular Transport, Pluripotent Stem Cells, CRISPR-Cas Systems

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Low Incidence of Off-Target Mutations in Individual CRISPR-Cas9 and TALEN Targeted Human Stem Cell Clones Detected by Whole-Genome Sequencing

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